Hydrochloric Acid → 2-Chloro-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-piperidin-1-ylpyridine-3,5-dicarbonitrile

HRID 1913500Notes

Reaction equation

HRID 1913500 reaction equation
N(OCCC(C)C)=O.N[C:10]1[C:15]([C:16]#[N:17])=[C:14]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:13]([C:24]#[N:25])=[C:12]([S:26][CH2:27][C:28]2[N:29]=[C:30]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=3)[S:31][CH:32]=2)[N:11]=1.[ClH:40]>C(#N)C.[Cu](Cl)Cl>[Cl:40][C:10]1[C:15]([C:16]#[N:17])=[C:14]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:13]([C:24]#[N:25])=[C:12]([S:26][CH2:27][C:28]2[N:29]=[C:30]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=3)[S:31][CH:32]=2)[N:11]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 24968474HCID 24968474, compound

Product 1

HCID 866400092-Chloro-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-piperidin-1-ylpyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

3.85 g (29.55 mmol) of isopentyl nitrite and 3.97 g (29.55 mmol) of copper(II) chloride were initially charged in 40 ml of acetonitrile, and 2.30 g (4.93 mmol) of the compound from Example 45A were added. The reaction mixture was stirred at 60° C. for 3 h. 20 ml of 1N hydrochloric acid were added to the reaction solution. The aqueous phase was extracted twice with in each case 40 ml of ethyl acetate. The combined organic phases were washed in each case once with 20 ml of saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed on a rotary evaporator. The residue was purified by column chromatography on silica gel 60 (mobile phase gradient cyclohexane:ethyl acetate=10:1→1:4).

Workup

  1. extractionThe aqueous phase was extracted twice with in each case 40 ml of ethyl acetate
  2. washThe combined organic phases were washed in each case once with 20 ml of saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was removed on a rotary evaporator
  5. customThe residue was purified by column chromatography on silica gel 60 (mobile phase gradient cyclohexane:ethyl acetate=10:1→1:4)

Sources & evidence

ORD record
ord-40deb0ca12aa404faa106610e316ebc9
Source dataset
uspto-grants-2013_12
Patent number
US08609686B2

Reaction notes

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